This A/SCOR, which is beginning its fifteenth year of funding, will continue to employ a multidisciplinary approach to elucidate factors involved in the pathogenesis of atherosclerosis. Studies will be carried out in the areas of lipid biochemistry, enzymology, diet-induced subhuman primate atherogenesis, morphometry, hemodynamics, eicosanoids, cell biology, molecular biology of the apolipoprotein genes, and pediatric epidemiology. A unique feature of our program is the availability of a large, well characterized pediatric and young adult population for epidemiologic and genetic studies, The Muscatine population. Another novel feature is the availability of a subhuman primate model for studies of lesion progression and regression in which morphometric analysis is correlated with hemodynamic changes and responses to neurocirculatory control mechanisms. A third unique aspect is the strong emphasis on arterial wall cell biology as it related to mechanisms involved in atherogenesis and its complications. In this regard many different kinds of cultured endothelial cells are continuously available for biochemical, immunological and structural studies. Our program consists of ten research projects and four core facilities. The projects deal with the incorporation of polyunsaturated fatty acids and their derivatives by endothelial cells; the membrane phospholipids of endothelial cells; protein phosphorylation as it relates to prostaglandin production by endothelial cells; the properties of cerebrovascular endothelium and smooth muscle; intracellular sorting and processing of lipids in relation to eicosanoid production; the role of lysosomal enzymes in intracellular lipid accumulation; the role of macrophage foam cells in arterial wall eicosanoid metabolism; morphometric changes in the arterial wall as a result of atherogenesis and during its regression; the effect of these changes on hemodynamics and responses to neuroendocrine regulation in specific vascular beds; the incidence, prevalence and tracking of atherogenic risk factors in a school age and young adult population, including genetic studies of restriction fragment length polymorphisms as risk factors for coronary artery disease. These project are supported by an administrative unit, a core lipid analysis laboratory, a core tissue culture facility and a core biostatistics unit.